Wang Jinfeng, Zhang Xin, Wang Lili, Yang Yongmei, Dong Zhaogang, Wang Haiyan, Du Lutao, Wang Chuanxin
Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, China; Department of Clinical Laboratory, Linyi People's Hospital, Linyi, Shandong Province, China.
Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
PLoS One. 2015 Feb 23;10(2):e0118086. doi: 10.1371/journal.pone.0118086. eCollection 2015.
MicroRNA-214 (miR-214) has been reported to be dysregulated in human bladder cancer tissues. We aimed to investigate the clinical correlation, biological significance and molecular network of miR-214 in bladder cancer. Our results showed miR-214 was down-regulated in bladder cancer tissues and significantly associated with tumor stage, lymph node status, grade, multifocality, history of non-muscle-invasive bladder cancer (NMIBC). Moreover, miR-214 could serve as an independent factor of recurrence-free survival (RFS) and overall survival (OS) for patients with muscle-invasive bladder cancer (MIBC). Restoration of miR-214 expression in bladder cancer cell lines inhibited cell proliferation, migration, invasion and markedly promoted apoptosis. Dual-luciferase reporter assay recognized PDRG1 as direct downstream target gene of miR-214. PDRG1 was significantly increased in tumors low of miR-214 and knockdown of PDRG1 mimicked the effects of miR-214 overexpression. Our findings manifest that miR-214 could exert tumor-suppressive effects in bladder cancer by directly down-regulating oncogene PDRG1 and suggest an appealing novel indicator for prognostic and therapeutic intervention of bladder cancer.
据报道,微小RNA-214(miR-214)在人类膀胱癌组织中表达失调。我们旨在研究miR-214在膀胱癌中的临床相关性、生物学意义及分子网络。我们的结果显示,miR-214在膀胱癌组织中表达下调,且与肿瘤分期、淋巴结状态、分级、多灶性、非肌层浸润性膀胱癌(NMIBC)病史显著相关。此外,miR-214可作为肌层浸润性膀胱癌(MIBC)患者无复发生存期(RFS)和总生存期(OS)的独立影响因素。在膀胱癌细胞系中恢复miR-214表达可抑制细胞增殖、迁移、侵袭,并显著促进细胞凋亡。双荧光素酶报告基因检测确定PDRG1为miR-214的直接下游靶基因。在miR-214低表达的肿瘤中,PDRG1显著上调,敲低PDRG1可模拟miR-214过表达的作用。我们的研究结果表明,miR-214可通过直接下调癌基因PDRG1在膀胱癌中发挥肿瘤抑制作用,并提示其可作为膀胱癌预后和治疗干预的一个有吸引力的新指标。